A New Positron Emission Tomography (PET) Radioligand for Imaging Sigma-1 Receptors in Living Subjects

Michelle L James; Bin Shen; Cristina L Zavaleta; Carsten Haagen Nielsen; Christophe Mésangeau; Pradeep K Vuppala; Carmel Chan; Bonnie A Avery; James A Fishback; Rae R Matsumoto; Sanjiv S Gambhir; Christopher R McCurdy; Frederick T Chin

doi:10.1021/jm300371c

A New Positron Emission Tomography (PET) Radioligand for Imaging Sigma-1 Receptors in Living Subjects

Michelle L James, Bin Shen, Cristina L Zavaleta, Carsten Haagen Nielsen, Christophe Mésangeau, Pradeep K Vuppala, Carmel Chan, Bonnie A Avery, James A Fishback, Rae R Matsumoto, Sanjiv S Gambhir, Christopher R McCurdy, Frederick T Chin

Biomedicinsk Institut

56 Citationer (Scopus)

Abstract

σ-1 receptor (S1R) radioligands have the potential to detect and monitor various neurological diseases. Herein we report the synthesis, radiofluorination, and evaluation of a new S1R ligand 6-(3-fluoropropyl)-3-(2- (azepan-1-yl)ethyl)benzo[d]thiazol-2(3H)-one ([¹⁸F]FTC-146, [ ¹⁸F]13). [¹⁸F]13 was synthesized by nucleophilic fluorination, affording a product with >99% radiochemical purity (RCP) and specific activity (SA) of 2.6 ± 1.2 Ci/μmol (n = 13) at end of synthesis (EOS). Positron emission tomography (PET) and ex vivo autoradiography studies of [¹⁸F]13 in mice showed high uptake of the radioligand in S1R rich regions of the brain. Pretreatment with 1 mg/kg haloperidol (2), nonradioactive 13, or BD1047 (18) reduced the binding of [¹⁸F]13 in the brain at 60 min by 80%, 82%, and 81%, respectively, suggesting that [ ¹⁸F]13 accumulation in mouse brain represents specific binding to S1Rs. These results indicate that [¹⁸F]13 is a promising candidate radiotracer for further evaluation as a tool for studying S1Rs in living subjects.

Originalsprog	Engelsk
Tidsskrift	Journal of Medicinal Chemistry
Vol/bind	55
Udgave nummer	19
Sider (fra-til)	8272-8282
Antal sider	11
ISSN	0022-2623
DOI	https://doi.org/10.1021/jm300371c
Status	Udgivet - 11 okt. 2012

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10.1021/jm300371c

Citationsformater

James, M. L., Shen, B., Zavaleta, C. L., Nielsen, C. H., Mésangeau, C., Vuppala, P. K., Chan, C., Avery, B. A., Fishback, J. A., Matsumoto, R. R., Gambhir, S. S., McCurdy, C. R., & Chin, F. T. (2012). A New Positron Emission Tomography (PET) Radioligand for Imaging Sigma-1 Receptors in Living Subjects. Journal of Medicinal Chemistry, 55(19), 8272-8282. https://doi.org/10.1021/jm300371c

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title = "A New Positron Emission Tomography (PET) Radioligand for Imaging Sigma-1 Receptors in Living Subjects",

abstract = "σ-1 receptor (S1R) radioligands have the potential to detect and monitor various neurological diseases. Herein we report the synthesis, radiofluorination, and evaluation of a new S1R ligand 6-(3-fluoropropyl)-3-(2- (azepan-1-yl)ethyl)benzo[d]thiazol-2(3H)-one ([18F]FTC-146, [ 18F]13). [18F]13 was synthesized by nucleophilic fluorination, affording a product with >99% radiochemical purity (RCP) and specific activity (SA) of 2.6 ± 1.2 Ci/μmol (n = 13) at end of synthesis (EOS). Positron emission tomography (PET) and ex vivo autoradiography studies of [18F]13 in mice showed high uptake of the radioligand in S1R rich regions of the brain. Pretreatment with 1 mg/kg haloperidol (2), nonradioactive 13, or BD1047 (18) reduced the binding of [18F]13 in the brain at 60 min by 80%, 82%, and 81%, respectively, suggesting that [ 18F]13 accumulation in mouse brain represents specific binding to S1Rs. These results indicate that [18F]13 is a promising candidate radiotracer for further evaluation as a tool for studying S1Rs in living subjects.",

author = "James, {Michelle L} and Bin Shen and Zavaleta, {Cristina L} and Nielsen, {Carsten Haagen} and Christophe M{\'e}sangeau and Vuppala, {Pradeep K} and Carmel Chan and Avery, {Bonnie A} and Fishback, {James A} and Matsumoto, {Rae R} and Gambhir, {Sanjiv S} and McCurdy, {Christopher R} and Chin, {Frederick T}",

year = "2012",

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doi = "10.1021/jm300371c",

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AU - James, Michelle L

AU - Shen, Bin

AU - Zavaleta, Cristina L

AU - Nielsen, Carsten Haagen

AU - Mésangeau, Christophe

AU - Vuppala, Pradeep K

AU - Chan, Carmel

AU - Avery, Bonnie A

AU - Fishback, James A

AU - Matsumoto, Rae R

AU - Gambhir, Sanjiv S

AU - McCurdy, Christopher R

AU - Chin, Frederick T

PY - 2012/10/11

Y1 - 2012/10/11

N2 - σ-1 receptor (S1R) radioligands have the potential to detect and monitor various neurological diseases. Herein we report the synthesis, radiofluorination, and evaluation of a new S1R ligand 6-(3-fluoropropyl)-3-(2- (azepan-1-yl)ethyl)benzo[d]thiazol-2(3H)-one ([18F]FTC-146, [ 18F]13). [18F]13 was synthesized by nucleophilic fluorination, affording a product with >99% radiochemical purity (RCP) and specific activity (SA) of 2.6 ± 1.2 Ci/μmol (n = 13) at end of synthesis (EOS). Positron emission tomography (PET) and ex vivo autoradiography studies of [18F]13 in mice showed high uptake of the radioligand in S1R rich regions of the brain. Pretreatment with 1 mg/kg haloperidol (2), nonradioactive 13, or BD1047 (18) reduced the binding of [18F]13 in the brain at 60 min by 80%, 82%, and 81%, respectively, suggesting that [ 18F]13 accumulation in mouse brain represents specific binding to S1Rs. These results indicate that [18F]13 is a promising candidate radiotracer for further evaluation as a tool for studying S1Rs in living subjects.

AB - σ-1 receptor (S1R) radioligands have the potential to detect and monitor various neurological diseases. Herein we report the synthesis, radiofluorination, and evaluation of a new S1R ligand 6-(3-fluoropropyl)-3-(2- (azepan-1-yl)ethyl)benzo[d]thiazol-2(3H)-one ([18F]FTC-146, [ 18F]13). [18F]13 was synthesized by nucleophilic fluorination, affording a product with >99% radiochemical purity (RCP) and specific activity (SA) of 2.6 ± 1.2 Ci/μmol (n = 13) at end of synthesis (EOS). Positron emission tomography (PET) and ex vivo autoradiography studies of [18F]13 in mice showed high uptake of the radioligand in S1R rich regions of the brain. Pretreatment with 1 mg/kg haloperidol (2), nonradioactive 13, or BD1047 (18) reduced the binding of [18F]13 in the brain at 60 min by 80%, 82%, and 81%, respectively, suggesting that [ 18F]13 accumulation in mouse brain represents specific binding to S1Rs. These results indicate that [18F]13 is a promising candidate radiotracer for further evaluation as a tool for studying S1Rs in living subjects.

U2 - 10.1021/jm300371c

DO - 10.1021/jm300371c

M3 - Journal article

C2 - 22853801

SN - 0022-2623

VL - 55

SP - 8272

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JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

IS - 19

ER -

A New Positron Emission Tomography (PET) Radioligand for Imaging Sigma-1 Receptors in Living Subjects

Abstract

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